The objectives of this project are to understand and modulate the course of development of amygdala-kindled seizures. The effects of carbamazepine and other anticonvulsants on amygdala kindling have been examined in relation to stage of kindled seizure development (as well as type of kindling stimulus; see Z01 MH 02528-01 BP). Agents with specific biological target systems have been used to attempt to modulate carbamazepine's anticonvulsant effects on kindled seizures, in order to elucidate carbamazepine's mechanisms of action. Finally, studies addressing possible mechanisms of amygdala kindling have been conducted with Mike Clark (For details of c-fos project, see Z01 MH 02460-02 BP), Mark Smith and Phil Gold (CNE Branch). Significant findings to date include demonstration of the following: 1) carbamazepine is an effective anticonvulsant agent during the completed phase of amygdala kindling, but not during seizure development; 2) valproic acid is an effective anticonvulsant agent against both seizure development and completed seizures; 3) carbamazepine's anticonvulsant effects can be reversed by agents that act at the peripheral benzodiazepine site (Ro5-4864) and the alpha-2-noradrenergic receptor (yohimbine); and 4) amygdala kindled seizures, electroconvulsive shock seizures, and afterdischarge activity in the amygdala (without generalized seizures) can induce CRH-mRNA in the hippocampus, in cells that do not normally express CRH message.